Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets to enhance potential for precision medicine. Here we describe the application of topological data analysis (TDA) for data-driven discovery in preclinical traumatic brain injury (TBI) and spinal cord injury (SCI) data sets mined from the Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization of inter-related histopathological, functional and health outcomes, TDA detected novel patterns across the syndromic network, uncovering interactions between SCI and co-occurring TBI, as well as detrimental drug effects in unpublished multicentre preclinical drug trial data in SCI. TDA also revealed that perioperative hypertension predicted long-term recovery better than any tested drug after thoracic SCI in rats. TDA-based data-driven discovery has great potential application for decision-support for basic research and clinical problems such as outcome assessment, neurocritical care, treatment planning and rapid, precision-diagnosis.

Efforts to understand spinal cord injury (SCI) and other complex neurotrauma disorders at the pre-clinical level have shown progress in recent years. However, successful translation of basic research into clinical practice has been slow, partly because of the large, heterogeneous data sets involved. In this sense, translational neurological research represents a "big data" problem. In an effort to expedite translation of pre-clinical knowledge into standards of patient care for SCI, we describe the development of a novel database for translational neurotrauma research known as Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI). We present demographics, descriptive statistics, and translational syndromic outcomes derived from our ongoing efforts to build a multi-center, multi-species pre-clinical database for SCI models. We leveraged archived surgical records, postoperative care logs, behavioral outcome measures, and histopathology from approximately 3000 mice, rats, and monkeys from pre-clinical SCI studies published between 1993 and 2013. The majority of animals in the database have measures collected for health monitoring, such as weight loss/gain, heart rate, blood pressure, postoperative monitoring of bladder function and drug/fluid administration, behavioral outcome measures of locomotion, and tissue sparing postmortem. Attempts to align these variables with currently accepted common data elements highlighted the need for more translational outcomes to be identified as clinical endpoints for therapeutic testing. Last, we use syndromic analysis to identify conserved biological mechanisms of recovery after cervical SCI between rats and monkeys that will allow for more-efficient testing of therapeutics that will need to be translated toward future clinical trials.

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OBJECTIVE With the recent evolution of endovascular therapies, objective evaluation of the efficacy of clip ligation for cerebral aneurysms should be performed. This study was undertaken to evaluate the durability of microsurgical clip ligation, identify risk factors for recurrence, and assess the need for long-term follow-up imaging. METHODS A retrospective review of medical records identified 616 consecutive patients (156 male and 460 female patients; mean age 48.4 ± 12.4 years; range 6-90 years) who underwent microsurgical clip ligation and follow-up imaging at least 1 year after discharge between 1990 and 2010 at our institution. Of a total of 926 aneurysms in 616 patients, 758 aneurysms were microsurgically clip-ligated. At presentation, 431 of these aneurysms were ruptured and 327 aneurysms were unruptured. All patients underwent postoperative baseline imaging within the 1st month of their operation. A logistic regression analysis was performed to identify which variables are more likely to predict recurrence. RESULTS Late follow-up angiographic imaging was obtained at a mean of 7.2 ± 4.7 years postdischarge (median 5.7 years; range 1-23 years). Of the 699 clipped aneurysms without residua, late follow-up angiography revealed only 1 (0.14%) recurrent aneurysm. Of the 59 residual aneurysms that remained after initial clip ligation on early postoperative imaging, 8 (13.6%) demonstrated growth. All of these aneurysms required treatment. None of the recurrences were due to broken or delayed displacement of clips. A total of 111 patients presented with multiple aneurysms. De novo aneurysm formation occurred in 8 (0.97%) patients, all of whom initially presented with multiple aneurysms. CONCLUSIONS This study provides additional evidence to support the long-term efficacy of aneurysm clip ligation. The chance of aneurysm recurrence after complete clip ligation is very small. However, there is a regrowth risk of 1.83% per year for aneurysm remnants after incomplete clip ligation. These findings support the necessity for continued followup, late angiographic imaging, and the potential need for further intervention of incompletely ligated aneurysms. Furthermore, completely clip-ligated aneurysms may not require additional surveillance imaging unless multiple aneurysms were evident at presentation.

OBJECTIVE Most patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) initially present to a hospital that lacks a neurosurgical unit. These patients require interhospital transfer (IHT) to tertiary facilities capable of multidisciplinary neurosurgical intervention. Yet, little is known about the effects of IHT on the outcomes of patients suffering from aSAH. In this study, the authors examined the effects of IHT and transport method on the timing of treatment, rebleed rates, and overall outcomes of patients who have experienced aSAH. METHODS A retrospective review of medical records identified all consecutive patients who presented with aSAH at an outside hospital and subsequently underwent IHT to a tertiary aneurysm care center and patients who initially presented directly to a tertiary aneurysm care facility between 2008 and 2015. Demographic, operative, radiological, hospital of initial evaluation, transfer method, and outcome data were retrospectively collected. RESULTS The authors identified 763 consecutive patients who were evaluated for aSAH at a tertiary aneurysm care facility either directly or following IHT. For patients who underwent IHT and after accounting for these patients' clinical variability and dichotomizing the patients into groups transferred less than 20 miles and more than 20 miles, the authors noted a significant increase in mortality rates: 7% (< 20 miles) and 18.8% (> 20 miles) (p = 0.004). The increased mortality rate was partially explained by an increased rate of initial presentation to an accredited stroke center in patients undergoing IHT of less than 20 miles (p = 0.000). The method of transport (ground or air ambulance) was found to have significant effect on the patients' outcomes as measured by the Glasgow Outcome Scale score (p = 0.021); patients who underwent ground transport demonstrated a higher likelihood of discharge to home (p = 0.004). The increased severity of presentation in the patient cohort undergoing IHT by air as defined by the Glasgow Coma Scale score, a need for an external ventricular drain, Hunt and Hess grade, and intubation status at presentation did not result in increased mortality when compared with the ground cohort (p = 0.074). In addition, there was an 8-hour increase in duration of time from admission to treatment for the air cohort as compared with the ground cohort (p = 0.054), indicating a potential for further improvement in the overall outcome of this patient group. CONCLUSIONS Aneurysmal SAH remains a challenging neurosurgical disease process requiring highly coordinated care in tertiary referral centers. In this study, the overall distance traveled and the transport method affected patient outcomes. The time from admission to treatment should continue to improve. Further analysis of IHT with a focus on patient monitoring and treatment during transport is warranted.

Recent preclinical advances highlight the therapeutic potential of treatments aimed at boosting regeneration and plasticity of spinal circuitry damaged by spinal cord injury (SCI). With several promising candidates being considered for translation into clinical trials, the SCI community has called for a non-human primate model as a crucial validation step to test efficacy and validity of these therapies prior to human testing. The present paper reviews the previous and ongoing efforts of the California Spinal Cord Consortium (CSCC), a multidisciplinary team of experts from 5 University of California medical and research centers, to develop this crucial translational SCI model. We focus on the growing volumes of high resolution data collected by the CSCC, and our efforts to develop a biomedical informatics framework aimed at leveraging multidimensional data to monitor plasticity and repair targeting recovery of hand and arm function. Although the main focus of many researchers is the restoration of voluntary motor control, we also describe our ongoing efforts to add assessments of sensory function, including pain, vital signs during surgery, and recovery of bladder and bowel function. By pooling our multidimensional data resources and building a unified database infrastructure for this clinically relevant translational model of SCI, we are now in a unique position to test promising therapeutic strategies’ efficacy on the entire syndrome of SCI. We review analyses highlighting the intersection between motor, sensory, autonomic and pathological contributions to the overall restoration of function.

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X-linked hypophosphatemia, due to PHEX mutations results in elevated fibroblast growth factor 23, hypophosphatemia and rickets/osteomalacia. Conventional therapy requires high doses of phosphate salts combined with active vitamin D analogues. Known complications of this regimen include nephrocalcinosis and secondary and tertiary hyperparathyroidism. The prevalence of hyperparathyroidism and treatment with parathyroidectomy in XLH is uncertain. The goal of this study was to estimate the prevalence of hyperparathyroidism and parathyroidectomy among XLH patients. We also characterized the outcome of parathyroidectomy for XLH patients. We conducted a retrospective chart review study from 1/1/2010 to 12/31/2017 using data from electronic records and paper charts. All XLH patients attending our center were eligible for analysis if they had at least one concurrent measurement of parathyroid hormone (PTH) and serum calcium. Categorization was based on the highest PTH and calcium values, persistence of hypercalcemia and a history of parathyroidectomy. Of the 104 patients having a diagnosis of XLH, 84 had concurrent measurements available of calcium and PTH. Data were available from 46 patients as adults and 43 as children (5 as both). Of these, 71/84 (84.52%), had evidence of secondary or tertiary hyperparathyroidism at any time point. Secondary hyperparathyroidism (defined as any PTH value ≥65pg/mL and not hypercalcemic) occurred in 35/43 (81.4%) children and 41/46 (89.1%) adults at any time point. Resolution of secondary hyperparathyroidism was observed in all children, except two with parathyroidectomies at ages 15 and 18 for tertiary hyperparathyroidism. Resolution of secondary hyperparathyroidism was observed in 27/41 adults. Tertiary (or hypercalcemic) hyperparathyroidism had an overall prevalence of 14/84 (16.67%) patients or 14/46 (30.4%) of adults (n=10 with PTH ≥65 pg/mL plus Calcium ≥10.5 mg/dl; n=1 with PTH ≥65 pg/mL plus Calcium 10.2-10.4 mg/dl; n=2 with PTH ≥50 pg/mL plus Calcium ≥10.5 mg/dL; n=1 with parathyroidectomy prior to presentation to our center). Parathyroidectomy was documented in 8/84 (9.5%) of the total population, or 8/46 (17.4%) of adults with XLH. After parathyroidectomy, residual or recurrent tertiary hyperparathyroidism was detected in 6/8 patients at a median of 6 years (ranging from 0 to 29 years). One patient had chronic postoperative hypoparathyroidism, and one patient remains normocalcemic 4 years after surgery. The majority of patients with XLH develop hyperparathyroidism during treatment with phosphate and active vitamin D. A significant proportion develop hypercalcemic hyperparathyroidism and most had recurrence of parathyroid autonomy after surgery. Careful monitoring and dose adjustment to minimize elevations of PTH are recommended.